The proposed research is part of an ongoing long-term experimental study of corneal diseases. The current main emphasis is on an investigation of corneal vascularization, corneal proteins in health and disease, and certain corneal dystrophies. Special attention would be devoted especially to macular, lattice and granular corneal dystrophies. The pathogenesis of corneal vascularization is being studied in vivo by evaluating variables that influence its severity, with particular attention to those of clinical significance. Corneal vascularization is being quantified in rodents in reproducible experimental models by using digitized images obtained from flat preparations of corneas with colloidal carbon filled blood vessels. To minimize individual host responses many experiments on corneal vascularization would be performed on inbred mice with the same genome. An attempt is also being made to quantify corneal neovascularization in living animals by using an image processor to digitize video images created by blood vessels. Part of this research would evaluate the relative roles of mediators of the inflammatory response as well as of cellular elements of the blood (polymorphonuclear leukocytes, lymphocytes, monocytes and platelets) and plasma constituents in the angiogenic response. An attempt would be made to detect putative angiogenic cytokines and growth factors in the cornea at the protein and mRNA levels prior to and during angiogenesis using immunochemical methods and the recently described techniques for quantification mRNA by the polymerase chain reaction. Other studies would focus on the major corneal soluble protein, which has an apparent molecular weight of 54,000 daltons and on diseases in which proteins accumulate within the cornea in pathologic states. The studies would involve state-of-the-art energy dispersive x-ray microanalytical and image processing equipment, cell and organ cultures, monoclonal antibodies, immunochemistry and sensitive biochemical and molecular biological analytical methods. A registry of known cases of muscular corneal dystrophy would be maintained and a genealogic and clinicopathologic investigation would be performed on these cases. Selected communities with a high gene frequency for macular corneal dystrophy would be screened for early cases with a sensitive ELISA technique that can detect keratan sulfate in serum and other body fluids. A registry of cases of granular and lattice corneal dystrophy would be expanded.
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